Autoantibody–Abzymes with Catalase Activity in Experimental Autoimmune Encephalomyelitis Mice

The exact mechanisms of the evolution of multiple sclerosis are still unknown. At the same time, the development in C57BL/6 mice of experimental autoimmune encephalomyelitis (EAE, simulating human multiple sclerosis) happens as a result of the violation of bone marrow hematopoietic stem cell differe...

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Main Authors: Andrey E. Urusov, Anna S. Tolmacheva, Kseniya S. Aulova, Georgy A. Nevinsky
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/28/3/1330
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author Andrey E. Urusov
Anna S. Tolmacheva
Kseniya S. Aulova
Georgy A. Nevinsky
author_facet Andrey E. Urusov
Anna S. Tolmacheva
Kseniya S. Aulova
Georgy A. Nevinsky
author_sort Andrey E. Urusov
collection DOAJ
description The exact mechanisms of the evolution of multiple sclerosis are still unknown. At the same time, the development in C57BL/6 mice of experimental autoimmune encephalomyelitis (EAE, simulating human multiple sclerosis) happens as a result of the violation of bone marrow hematopoietic stem cell differentiation profiles integrated with the production of toxic auto-antibodies splitting the basic myelin protein, myelin oligodendrocyte glycoprotein (MOG), histones, and DNA. It has been shown that IgGs from the plasma of healthy humans and autoimmune patients oxidize many different compounds due to their peroxidase (H<sub>2</sub>O<sub>2</sub>-dependent) and oxidoreductase (H<sub>2</sub>O<sub>2</sub>-independent) activities. Here, we first analyzed the changes in the relative catalase activity of IgGs from C57BL/6 mice blood plasma over time at different stages of the EAE development (onset, acute, and remission phases). It was shown that the catalase activity of IgGs of 3-month-old mice is, on average, relatively low (<i>k</i><sub>cat</sub> = 40.7 min<sup>−1</sup>), but it increases during 60 days of spontaneous development of EAE 57.4-fold (<i>k</i><sub>cat</sub> = 2.3 × 10<sup>3</sup> min<sup>−1</sup>). The catalase activity of antibodies increases by a factor of 57.4 by 20 days after the immunization of mice with MOG (<i>k</i><sub>cat</sub> = 2.3 × 10<sup>3</sup> min<sup>−1</sup>), corresponding to the acute phase of EAE development, and 52.7–fold by 60 days after the treatment of mice with a DNA–histone complex (<i>k</i><sub>cat</sub> = 2.1 × 10<sup>3</sup> min<sup>−1</sup>). It is the acceleration of the EAE development after the treatment of mice with MOG that leads to the increased production of lymphocytes synthesizing antibodies with catalase activity. All data show that the IgGs’ catalase activity can play an essential role in reducing the H<sub>2</sub>O<sub>2</sub> concentration and protecting mice from oxidative stress.
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spelling doaj.art-c53eb8588f2c43538722f5ded080e5c22023-11-16T17:30:56ZengMDPI AGMolecules1420-30492023-01-01283133010.3390/molecules28031330Autoantibody–Abzymes with Catalase Activity in Experimental Autoimmune Encephalomyelitis MiceAndrey E. Urusov0Anna S. Tolmacheva1Kseniya S. Aulova2Georgy A. Nevinsky3Institute of Chemical Biology and Fundamental Medicine, SB of the Russian Academy of Sciences, Lavrentiev Ave., 8, Novosibirsk 630090, RussiaInstitute of Chemical Biology and Fundamental Medicine, SB of the Russian Academy of Sciences, Lavrentiev Ave., 8, Novosibirsk 630090, RussiaInstitute of Chemical Biology and Fundamental Medicine, SB of the Russian Academy of Sciences, Lavrentiev Ave., 8, Novosibirsk 630090, RussiaInstitute of Chemical Biology and Fundamental Medicine, SB of the Russian Academy of Sciences, Lavrentiev Ave., 8, Novosibirsk 630090, RussiaThe exact mechanisms of the evolution of multiple sclerosis are still unknown. At the same time, the development in C57BL/6 mice of experimental autoimmune encephalomyelitis (EAE, simulating human multiple sclerosis) happens as a result of the violation of bone marrow hematopoietic stem cell differentiation profiles integrated with the production of toxic auto-antibodies splitting the basic myelin protein, myelin oligodendrocyte glycoprotein (MOG), histones, and DNA. It has been shown that IgGs from the plasma of healthy humans and autoimmune patients oxidize many different compounds due to their peroxidase (H<sub>2</sub>O<sub>2</sub>-dependent) and oxidoreductase (H<sub>2</sub>O<sub>2</sub>-independent) activities. Here, we first analyzed the changes in the relative catalase activity of IgGs from C57BL/6 mice blood plasma over time at different stages of the EAE development (onset, acute, and remission phases). It was shown that the catalase activity of IgGs of 3-month-old mice is, on average, relatively low (<i>k</i><sub>cat</sub> = 40.7 min<sup>−1</sup>), but it increases during 60 days of spontaneous development of EAE 57.4-fold (<i>k</i><sub>cat</sub> = 2.3 × 10<sup>3</sup> min<sup>−1</sup>). The catalase activity of antibodies increases by a factor of 57.4 by 20 days after the immunization of mice with MOG (<i>k</i><sub>cat</sub> = 2.3 × 10<sup>3</sup> min<sup>−1</sup>), corresponding to the acute phase of EAE development, and 52.7–fold by 60 days after the treatment of mice with a DNA–histone complex (<i>k</i><sub>cat</sub> = 2.1 × 10<sup>3</sup> min<sup>−1</sup>). It is the acceleration of the EAE development after the treatment of mice with MOG that leads to the increased production of lymphocytes synthesizing antibodies with catalase activity. All data show that the IgGs’ catalase activity can play an essential role in reducing the H<sub>2</sub>O<sub>2</sub> concentration and protecting mice from oxidative stress.https://www.mdpi.com/1420-3049/28/3/1330EAE modelC57BL/6 micecatalytic antibodiescatalase activity
spellingShingle Andrey E. Urusov
Anna S. Tolmacheva
Kseniya S. Aulova
Georgy A. Nevinsky
Autoantibody–Abzymes with Catalase Activity in Experimental Autoimmune Encephalomyelitis Mice
Molecules
EAE model
C57BL/6 mice
catalytic antibodies
catalase activity
title Autoantibody–Abzymes with Catalase Activity in Experimental Autoimmune Encephalomyelitis Mice
title_full Autoantibody–Abzymes with Catalase Activity in Experimental Autoimmune Encephalomyelitis Mice
title_fullStr Autoantibody–Abzymes with Catalase Activity in Experimental Autoimmune Encephalomyelitis Mice
title_full_unstemmed Autoantibody–Abzymes with Catalase Activity in Experimental Autoimmune Encephalomyelitis Mice
title_short Autoantibody–Abzymes with Catalase Activity in Experimental Autoimmune Encephalomyelitis Mice
title_sort autoantibody abzymes with catalase activity in experimental autoimmune encephalomyelitis mice
topic EAE model
C57BL/6 mice
catalytic antibodies
catalase activity
url https://www.mdpi.com/1420-3049/28/3/1330
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AT annastolmacheva autoantibodyabzymeswithcatalaseactivityinexperimentalautoimmuneencephalomyelitismice
AT kseniyasaulova autoantibodyabzymeswithcatalaseactivityinexperimentalautoimmuneencephalomyelitismice
AT georgyanevinsky autoantibodyabzymeswithcatalaseactivityinexperimentalautoimmuneencephalomyelitismice